Acquired immune deficiency syndrome (AIDS) is recognized as an epidemic in several areas of the world, including the United States. The Human Immunodeficiency Virus (HIV-1), a retrovirus, has been identified as the etiologic cause of the disease. HIV-1 was previously identified as Human T-Cell Lymphotropic Virus Type III (HTLV-III) and Lymphadenopathy Associated Virus (LAV). The groups at highest risk of infection with HIV-1 include homosexual and bisexual men and abusers of injected drugs. Other predictable high-risk groups are women artificially inseminated with sperm from infected donors and sexual partners of those in the AIDS risk groups. Recipients of blood transfusions, blood products or organs are also at risk of contracting AIDS. There is also evidence that HIV-1 is transmitted heterosexually as a result of sexual contact.
Known therapies are generally limited to regimens designed to treat the opportunistic infections and neoplasias associated with AIDS and its related illnesses. Very few treatments are available, however, which are directed towards the virus itself. Among the known antiviral drugs, which are believed to merely slow down viral replication and which do not cure the disease, much less prevent reinfection, are azidothymidine (AZT), alpha interferon, gamma interferon, azimexon and isopinosine. Remission of some Karposi sarcomas has been reported following treatment with alpha interferon, but the other antiviral drugs have not proven effective against HIV-1 infections. Immunomodulators, such as cimetidine and interleukin-2, which are intended to stimulate natural killer cell activity, have been reported as useful in the treatment of AIDS. Similar claims have also been made in connection with indomethacin, an antiinflammatory and prostaglandin inhibitor. In summary, current methods for treating individuals infected with HIV-1 are few, and largely ineffective.
Some therapeutic success has been observed following intravenous immunoglobulin treatment of HIV-infected children (Clavelli et al., Pediatr. Infec. Dis. 5:S207 (1986)). It has been proposed that this treatment may be particularly beneficial to HIV-infected children. These children exhibit increased susceptibility to bacterial and viral infections due to both the destructive effects of HIV-1 infection and because infants possess an immature immune system. Specific anti-HIV-1 antibodies may have protective effects against infection. Passive administration of immunoglobulin from asymptomatic, HIV-1 positive individuals has led to a temporary clinical improvement in these individuals (Wendler et al., AIDS Res. and Hum. Retroviruses 3:177 (1987) and Rank et al., Clin Exp. Immunol. 69:231 (1987)). Another study has shown that children born to HIV-1 positive mothers were less likely to be infected with HIV-1 if they possessed serum with high neutralizing activity (Broliden et al., AIDS 3:577 (1989)). This indicates the presence of maternal antibodies which may confer protection when passed from mother to child. However, transfusion of serum from HIV-1 infected individuals is not feasible on a large scale, and administration of mouse monoclonal antibodies may be ineffective due to anti-murine immune responses in human patients.
While passive administration of protective immunoglobulin to HIV-1 infected patients is worthy of investigation, there are several obstacles to the production of such antibodies. Currently the only source of such antisera are from already infected individuals. Collection of their antisera presents risks to themselves and health care workers. In addition such immunoglobulin may contain virus particles which could be infectious to treated populations, thus complicating their production if not ultimately patient therapy.